Process for cyclizing optically active 4-amino-2-halogenobutyric acids

ABSTRACT

The invention provides a process for producing optically active azetidine-2-carboxylic acid with good efficiency, expedience, and commercial advantage,  
     which comprises cyclizing an optically active 4-amino-2-halogenobutyric acid in an optical yield of as high as 90% or more.  
     It is a process for producing optically active azetidine-2-carboxylic acid of the general formula (2), in which * denotes an asymmetric carbon atom,  
     which comprises cyclizing an optically active 4-amino-2-halogenobutyric acid of the general formula ( 1 ), in which X represents a halogen atom and * denotes an asymmetric carbon atom,  
     in the presence of an oxide of an alkaline earth metal, a hydroxide of an alkaline earth metal excepting barium, or an organic amine.

TECHNICAL FIELD

[0001] The present invention relates to a process for producing anoptically active azetidine-2-carboxylic acid, which is of value as aproduction intermediate of pharmaceuticals or the like, through thecyclization of an optically active 4-amino-2-halogenobutyric acid.

BACKGROUND ART

[0002] The following processes are known for the production ofazetidine-2-carboxylic acid through utilization of the cyclizationreaction of a 4-amino-2-halogenobutyric acid.

[0003] (1) A process which comprises subjecting hydrochloricacid-nitrous acid to act on (S)-2,4-diaminobutyric acid to give(S)-4-amino-2-chlorobutyric acid and, then, heating it in an aqueoussolution of barium hydroxide to give (R)-azetidine-2-carboxylic acid(Biochemical Journal, 64, 323 (1956)).

[0004] (2) A process which comprises subjecting dimethyl sulfate to acton pyrrolidin-2-one to give methoxyimine, brominating it withN-bromosuccinimide, hydrolyzing the same to DL-4-amino-2-bromobutyricacid, and heat-treating it in an aqueous solution of barium hydroxide orsodium hydroxide to give DL-azetidine-2-carboxylic acid (Agriculturaland Biological Chemistry, 37, 649 (1973).

[0005] However, the above processes have the following drawbacks.

[0006] In process (1) wherein the cyclization reaction is conductedunder heating at a high temperature in an aqueous solution of bariumhydroxide, the optically active compound undergoes racemization todrastically reduce the optical purity of the product. Of the productwith such a drastically reduced optical purity, one of the enantiomersis generally unwanted and an optical resolution or the like procedure isrequired for improving the optical purity. Moreover, the unwantedenantiomer so separated has to be discarded unless a profitableracemization method is available, with the result that the process isnot economical and does not lend itself well to commercial production.

[0007] In process (2), the product azetidine-2-carboxylic acid is aracemic compound and the resolution of this racemic compound isnecessary for obtaining the optically active compound. Moreover, afterresolution the unwanted enantiomer has to be discarded unless aprofitable racemization method is available so that this process is noteconomical and does not lend itself well to commercial production.

SUMMARY OF THE INVENTION

[0008] In view of the above state of the art, the present invention hasits object to provide an efficient, economical and commerciallyprofitable process for producing an optically activeazetidine-2-carboxylic acid.

[0009] The inventors of the present invention did much research forovercoming the above-mentioned disadvantages and have ultimatelydeveloped the present invention.

[0010] The present invention, therefore, is directed to a process forproducing optically active azetidine-2-carboxylic acid of the generalformula (2):

[0011] (wherein * denotes an asymmetric carbon atom) which comprisescyclizing an optically active 4-amino-2-halogenobutyric acid representedby the general formula (1):

[0012] (wherein X represents a halogen atom; * denotes an asymmetriccarbon atom) in the presence of an oxide of an alkaline earth metal, ahydroxide of an alkaline earth metal excepting barium, or an organicamine. In accordance with the present invention, there is provided aprocess for producing optically active azetidine-2-carboxylic acid inhigh optical yield.

[0013] The present invention is now described in detail.

DISCLOSURE OF INVENTION

[0014] The starting material of the invention, namely an opticallyactive 4-amino-2-halogenobutyric acid, may be whichever of the pure(R)-compound and the pure (S)-compound or a mixture of these compoundscontaining either enantiomer in excess but for the production ofoptically active azetidine-2-carboxylic acid, the material of highoptical purity is, of course, preferred. Moreover, the halogen atom ofsaid optically active 4-amino-2-halogenobutyric acid may be a fluorine,a chlorine, a bromine or an iodine atom but is preferably a chlorine ora bromine atom.

[0015] As such an optically active 4-amino-2-halogenobutyric acid,(S)-4-amino-2-chlorobutyric acid, for instance, can be obtained from(S)-2,4-diaminobutyric acid by the process described in BiochemicalJournal, 64, 323 (1956). Moreover, by the process described in JPAHei-11-169620, an (R)-4-amino-2-halogenobutyric acid ester can behydrolyzed in an aqueous solution of a mineral acid to give ahydrolyzate solution containing an (R)-4-amino-2-halogenobutyric acid.This hydrolyzate solution may be neutralized with an alkali metal base,for instance, and directly submitted to the cyclization reaction or theneutralized solution may further be purified by ion exchange columnchromatography to isolate the optically active(R)-4-amino-2-halogenobutyric acid.

[0016] The optically active 4-amino-2-halogenobutyric acid of generalformula (1), thus obtained, can be cyclized in the presence of a base,such as an oxide of an alkaline earth metal, a hydroxide of an alkalineearth metal excepting barium, or an organic amine to produce opticallyactive azetidine-2-carboxylic acid of general formula (2) in goodoptical yield.

[0017] The oxide of an alkaline earth metal which can be used in thecyclization reaction includes magnesium oxide, calcium oxide, bariumoxide, etc., with magnesium oxide being particularly preferred. Thehydroxide of an alkaline earth metal includes magnesium hydroxide,calcium hydroxide, etc., although magnesium hydroxide is particularlypreferred.

[0018] As the organic amine, a secondary amine or a tertiary amine canbe used with advantage. Among preferred examples are secondaryalkylamines such as dimethylamine, diethylamine, dipropylamine,diisopropylamine, dibutylamine, diisobutylamine, di-sec-butylamine,di-tert-butylamine, dipentylamine, dihexylamine, diheptylamine,dioctylamine, dicyclohexylamine, etc.; secondary cycloalkylamines suchas piperidine, piperazine, 2,2,6,6-tetramethylpiperidine, etc.;secondary arylamines such as diphenylamine, ditolylamine, etc.;secondary arylalkylamines such as dibenzylamine etc.; tertiaryalkylamines such as trimethylamine, triethylamine, tripropylamine,triisopropylamine, tributylamine, triisobutylamine,diisopropylethylamine, diisobutylmethylamine,N,N-diethyl-tert-octylamine, etc.; tertiary cycloalkylamines such as4-(dimethylamino)-1,2,2,6,6-pentamethylpiperidine etc.; tertiaryarylamines such as triphenylamine, tritolylamine, etc.; tertiaryarylalkylamines such as tribenzylamine etc.; polycyclic tertiarycycloamines such as 1,8-diazabicylo[4.5.0]undecene,1,5-diazabicyclo[4.3.0]nonene, 1,4-diazabicyclo[2.2.2]octane, etc.; andtertiary aminealcohols such as N,N-dimethylethanolamine,N,N-diethylethanolamine, N,N-dipropylethanolamine, etc., althoughdiisopropylamine, 2,2,6,6-tetramethylpiperidine, triethylamine,diisopropylethylamine, 1,8-diazabicyclo[4.5.0]undecene, andN,N-dimethylethanolamine are particularly preferred.

[0019] The level of use of said base is not particularly restricted butthe cyclization reaction can be carried out generally in the presence of1 to 30 molar equivalents of the base relative to the optically active4-amino-2-halogenobutyric acid (1). The generally preferred level is 1to 10 molar equivalents.

[0020] For the above cyclization reaction, a solvent is generallyemployed. This solvent is preferably water or a mixture of water and awater-soluble organic solvent which is freely miscible with water. Thewater-soluble organic solvent mentioned just above includes methanol,ethanol, isopropyl alcohol, tert-butyl alcohol, acetone, acetonitrile,N,N-dimethylformamide and N,N-dimethylacetamide, to mention just a fewexamples. The organic solvent can be used in a proportion of 1 to 100volume %, preferably 1 to 50 volume %, relative to water.

[0021] The concentration of the optically active4-amino-2-halogenobutyric acid (1) in the cyclization reaction system isgenerally 0.5 to 50 weight %, preferably 1 to 30 weight %.

[0022] The cyclization reaction temperature varies with different typesof base used but is usually within the range of the freezing point tothe boiling point of the reaction solvent, namely water or mixture ofwater and a water-soluble organic solvent. To allow the reaction to goto completion in a short time, the reaction is preferably conducted at ahigh temperature, but for preventing racemization during the reaction,the reaction temperature is preferably low. Generally speaking, thereaction temperature is 30 to 100° C., more preferably 50 to 100° C.

[0023] The cyclization reaction time depends on the type and equivalentof said base and the reaction temperature, but assuming that thereaction temperature is 80 to 100° C., for instance, the reaction can beusually carried to completion in about 20 minutes to about 12 hours.

[0024] While the cyclization reaction can be conducted under the aboveconditions, this cyclization reaction is a substitution cyclizationreaction involving a stereochemical inversion of the halogen substituentin the 2-position of the optically active 4-amino-2-halogenobutyric acid(1) and gives rise to the (R)-form of azetidine-2-carboxylic acid fromthe (S)-form of the staring compound or the (S) form ofazetidine-2-carboxylic acid from the (R)-form of the starting compound.Moreover, by adjusting the reaction conditions judiciously, the opticalyield of this cyclization reaction can be increased to as high as 90% ormore. The term “optical yield” as used herein means the percentage ofthe optical purity (enantiomeric excess, % ee) of the reaction productoptically active azetidine-2-carboxylic acid relative to the opticalpurity (enantiomeric excess, % ee) of the starting material opticallyactive 4-amino-2-halogenobutyric acid.

[0025] Referring to the isolation of the reaction product aftercompletion of the above cyclization reaction, taking the case in whichan inorganic base is used as an example, the objective optically activeazetidine-2-carboxylic acid can be isolated by neutralizing the basewith an acid in the first place and purifying the reaction mixture byion exchange column chromatography. In the case where an organic amineis used, the optically active azetidine-2-carboxylic acid can beisolated by subjecting the reaction mixture to phase separation toremove the residual organic amine as an organic layer and then purifyingthe aqueous layer by ion exchange column chromatography. Furthermore,where necessary, the optical purity can be increased by crystallization.

[0026] Moreover, the cyclization reaction mixture may be directlysubjected to an amino-protecting reaction bypassing isolation of thecyclization product and the resulting amino-protected optically activeazetidine-2-carboxylic acid derivative be isolated by the routineprocedure such as extraction, concentration, chromatography, and/orcrystallization.

BEST MODE FOR CARRYING OUT THE INVENTION

[0027] The following examples illustrate the present invention infurther detail without defining the scope of the invention.

EXAMPLE 1

[0028] To 27.6 ml of an aqueous solution containing 350.8 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 78.4% ee) was added157.2 mg of magnesium oxide, and the reaction was carried out at 90° C.for 3 hours. Without isolating the (S)-azetidine-2-carboxylic acidformedinthereaction mixture, 2.5 ml of di-tert-butyl dicarbonate wasadded to the reaction mixture and the reaction was further conducted atroom temperature overnight. This reaction mixture was adjusted to pH 2.0with 6N-hydrochloric acid and extracted with 3 portions of ethylacetate. The organic layer was washed with a saturated aqueous solutionof sodium chloride and dried over anhydrous sodium sulfate, and thesolvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 60.2%,optical purity 76.3% ee, optical yield 97.3%).

[0029]¹H-NMR (CDCl₃) δ 1.48 (s, 9H), 2.40-2.60 (bs, 2H), 3.80-4.00 (bs,2H), 4.80 (t, 1H)

[0030]¹³C-NMR (CDCl₃) δ 19.9, 28.3, 47.2, 60.4, 81.6, 157.3, 173.5

[0031] The yield was determined by high performance liquidchromatography using a high-purity product of(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid as a standard.The optical purity was determined by high performance liquidchromatography under the following conditions.

[0032] HPLC (Condition for Optical Purity Analysis)

[0033] Column: Chiral Cell OD-R (Daicel), 4.6 mm in. dia. ×25 cm long

[0034] Eluent: acetonitrile/perchloric acid aq. sol. (pH 2.0)=1/6

[0035] Column flow rate: 0.7 ml/min.

[0036] Column temperature: 30° C.

[0037] Detection wavelength: UV210 nm

[0038] Retention time: (S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylicacid: ca 35 min; (R)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid:ca 40 min.

EXAMPLE 2

[0039] To 6.85 ml of an aqueous solution containing 365.4 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 94.2% ee) was added232.8 mg of magnesium hydroxide, and the reaction was conducted at 90°C. for 7 hours. Without isolating the (S)-azetidine-2-carboxylic acidformed in the reaction mixture, 1.13 g of sodium carbonate and 1.2 ml ofdi-tert-butyl dicarbonate were added to the reaction mixture and thereaction was further carried out at room temperature overnight. Thisreaction mixture was adjusted to pH 2.0 with 6N-hydrochloric acid andextracted with 3 portions of ethyl acetate. The organic layer was washedwith a saturated aqueous solution of sodium chloride and dried overanhydrous sodium sulfate. The solvent was then distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 34.8%,optical purity 90.0% ee, optical yield 96.8%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 3

[0040] To 27.6 ml of an aqueous solution containing 350.8 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 78.4% ee) was added1.43 ml of diisopropylamine, and the reaction was carried out at 90° C.for 3 hours. Without isolating the (S)-azetidine-2-carboxylic acidformed in the reaction mixture, 2.5 ml of di-tert-butyl dicarbonate wasadded to the reaction mixture and the reaction was further conducted atroom temperature overnight. This reaction mixture was adjusted to pH 2.0with 6N-hydrochloric acid and extracted with 3 portions of ethylacetate. The organic layer was washed with a saturated aqueous solutionof sodium chloride and dried over anhydrous sodium sulfate, and thesolvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 55.2%,optical purity 75.7% ee, optical yield 96.5%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 4

[0041] To 30.5 ml of an aqueous solution containing 348.0 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 92.9% ee) was added1.77 ml of 2,2,6,6-tetramethylpiperidine, and the reaction was carriedout at 90° C. for 2.75 hours. Without isolating the(S)-azetidine-2-carboxylic acid formed in the reaction mixture, 2.6 mlof di-tert-butyl dicarbonate was added to the reaction mixture and thereaction was further conducted at room temperature overnight. Thisreaction mixture was adjusted to pH 2.0 with 6N-hydrochloric acid andextracted with 3 portions of ethyl acetate. The organic layer was washedwith a saturated aqueous solution of sodium chloride and dried overanhydrous sodium sulfate, and the solvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 57.3%,optical purity 88.6% ee, optical yield 95.3%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 5

[0042] To 30.8 ml of an aqueous solution containing 361.8 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 92.9% ee) was added1.83 ml of diisopropylethylamine, and the reaction was carried out at90° C. for 4 hours. Without isolating the (S)-azetidine-2-carboxylicacid formed in the reaction mixture, 1.3 ml of di-tert-butyl dicarbonatewas added to the reaction mixture and the reaction was further conductedat room temperature overnight. This reaction mixture was adjusted to pH2.0 with 6N-hydrochloric acid and extracted with 3 portions of ethylacetate. The organic layer was washed with a saturated aqueous solutionof sodium chloride and dried over anhydrous sodium sulfate, and thesolvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 48.1%,optical purity 89.0% ee, optical yield 95.8%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 6

[0043] To 30.0 ml of an aqueous solution containing 375.5 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 92.9% ee) was added1.57 ml of 1,8-diazabicyclo[4.5.0]undecene, and the reaction was carriedout at 90° C. for 3.5 hours. Without isolating the(S)-azetidine-2-carboxylic acid formed in the reaction mixture, 1.3 mlof di-tert-butyl dicarbonate was added to the reaction mixture and thereaction was further conducted at room temperature overnight. Thisreaction mixture was adjusted to pH 2.0 with 6N-hydrochloric acid andextracted with 3 portions of ethyl acetate. The organic layer was washedwith a saturated aqueous solution of sodium chloride and dried overanhydrous sodium sulfate, and the solvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 49.4%,optical purity 87.1% ee, optical yield 93.8%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 7

[0044] To 30.0 ml of an aqueous solution containing 374.1 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 92.9% ee) was added1.09 ml of N,N-dimethylethanolamine, and the reaction was carried out at90° C. for 3.5 hours. Without isolating the (S)-azetidine-2-carboxylicacid formed in the reaction mixture, 1.3 ml of di-tert-butyl dicarbonatewas added to the reaction mixture and the reaction was further conductedat room temperature overnight. This reaction mixture was adjusted to pH2.0 with 6N-hydrochloric acid and extracted with 3 portions of ethylacetate. The organic layer was washed with a saturated aqueous solutionof sodium chloride and dried over anhydrous sodium sulfate, and thesolvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 32.3%,optical purity 86.8% ee, optical yield 93.4%). The yield and opticalpurity were determined in the same manner as in Example 1.

EXAMPLE 8

[0045] To 27.6 ml of an aqueous solution containing 350.8 mg of(R)-4-amino-2-chlorobutyric acid (optical purity 78.4% ee) was added1.50 ml of triethylamine, and the reaction was carried out at 90° C. for3 hours and 20 minutes. Without isolating the (S)-azetidine-2-carboxylicacid formed in the reaction mixture, 1.3 ml of di-tert-butyl dicarbonatewas added to the reaction mixture and the reaction was further conductedat room temperature overnight. This reaction mixture was adjusted to pH2.0 with 6N-hydrochloric acid and extracted with 3 portions of ethylacetate. The organic layer was washed with a saturated aqueous solutionof sodium chloride and dried over anhydrous sodium sulfate, and thesolvent was distilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 51.1%,optical purity 71.2% ee, optical yield 90.8%). The yield and opticalpurity were determined in the same manner as in Example 1.

COMPARATIVE EXAMPLE 1

[0046] To 400 ml of an aqueous solution containing 9.36 g of(R)-4-amino-2-chlorobutyric acid (optical purity 78.4% ee) was added43.4 g of barium hydroxide octahydrate, and the reaction was carried outat 90° C. for 2 hours. Without isolating the (S)-azetidine-2-carboxylicacid formed in the reaction mixture, the reaction mixture was adjustedto pH 7.0 with concentrated hydrochloric acid and 50.5 g of sodiumcarbonate and 31.6 g of di-tert-butyl dicarbonate were serially added tothe reaction mixture. The reaction was then carried out at roomtemperature overnight. This reaction mixture was adjusted to pH 2.0 with6N-hydrochloric acid and extracted with 3 portions of ethyl acetate. Theorganic layer was washed with a saturated aqueous solution of sodiumchloride and dried over anhydrous sodium sulfate, and the solvent wasdistilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 52.6%,optical purity 63.7% ee, optical yield 81.3%). The yield and opticalpurity were determined in the same manner as in Example 1.

COMPARATIVE EXAMPLE 2

[0047] To 400 ml of an aqueous solution containing 9.36 g of(R)-4-amino-2-chlorobutyric acid (optical purity 78.4% ee) was added 11g of sodium hydroxide, and the reaction was carried out at 90° C. for 4hours. Without isolating the (S)-azetidine-2-carboxylic acid formed inthe reaction mixture, the reaction mixture was adjusted to pH 7.0 withconcentrated hydrochloric acid and 64.9 g of sodium carbonate and 31.6 gof di-tert-butyl dicarbonate were serially added to the reactionmixture. The reaction was then carried out at room temperatureovernight. This reaction mixture was adjusted to pH 2.0 with6N-hydrochloric acid and extracted with 3 portions of ethyl acetate. Theorganic layer was washed with a saturated aqueous solution of sodiumchloride and dried over anhydrous sodium sulfate, and the solvent wasdistilled off to obtain(S)-N-(tert-butoxycarbonyl)azetidine-2-carboxylic acid (yield 48.0%,optical purity 56.4% ee, optical yield 71.9%). The yield and opticalpurity were determined in the same manner as in Example 1.

REFERENCE EXAMPLE 1

[0048] Synthesis of (R)-4-amino-2-chlorobutyric Acid

[0049] In 1900 ml of 1M aqueous sulfuric acid was dissolved 38 g ofmethyl (R)-4-amino-2-chlorobutyrate (optical purity 79.1% ee), and thereaction was conducted at room temperature for 72 hours. This reactionmixture was neutralized with 210 g of sodium carbonate, whereby anaqueous solution of (R)-4-amino-2-chlorobutyric acid was obtained inquantitative yield (optical purity 78.4% ee). This reaction mixture wasdirectly subjected to cyclization reaction.

REFERENCE EXAMPLE 2

[0050] In 45 ml of 1M aqueous sulfuric acid was dissolved 4.53 g ofmethyl (R)-4-amino-2-chlorobutyrate (optical purity 94.2% ee), and thereaction was conducted at room temperature for 48 hours as in ReferenceExample 1. This reaction mixture was neutralized with sodium carbonateto give an aqueous solution of (R)-4-amino-2-chlorobutyric acid inquantitative yield (optical purity 94.2% ee) This reaction mixture wassubjected to cyclization reaction, as diluted at each time of use.

INDUSTRIAL APPLICABILITY

[0051] In accordance with the production process of the invention, anoptically active 4-amino-2-halogenobutyric acid can be cyclized in thepresence of an oxide of an alkaline earth metal, a hydroxide of analkaline earth metal excepting barium, or an organic amine to produceoptically active azetidine-2-carboxylic acid in an optical yield of ashigh as 90% or more with good efficiency, expedience, and commercialadvantage.

1. A process for producing an optically active azetidine-2-carboxylicacid of the general formula (2):

in the formula, * denotes an asymmetric carbon atom, which comprisescyclizing an optically active 4-amino-2-halogenobutyric acid of thegeneral formula (1):

 in the formula, X represents a halogen atom and * denotes an asymmetriccarbon atom, in the presence of an oxide of an alkaline earth metal, ahydroxide of an alkaline earth metal excepting barium, or an organicamine.
 2. The process according to claim 1, wherein the oxide of analkaline earth metal is magnesium oxide.
 3. The process according toclaim 1, wherein the hydroxide of an alkaline earth metal is magnesiumhydroxide.
 4. The process according to claim 1, wherein the organicamine is a secondary amine or a tertiary amine.
 5. The process accordingto claim 4, wherein the secondary amine is 2,2,6,6-tetramethylpiperidineor diisopropylamine and the tertiary amine is diisopropylethylamine,triethylamine, 1,8-diazabicyclo[4.5.0]undecene, orN,N-dimethylethanolamine.
 6. The process according to any of claims 1 to5, wherein the halogen atom is a chlorine or a bromine atom.
 7. Theprocess according to any of claims 1 to 6, wherein water or a mixture ofwater and a water-soluble organic solvent is used as a solvent forcyclization reaction.
 8. The process according to any of claims 1 to 7,wherein an optical yield of the cyclization reaction is not less than90%.